Paracellular transport of phosphate along the intestine

Inorganic phosphate (P-i) is crucial for many biological functions, such as energy metabolism, signal transduction, and pH buffering. Efficient systems must exist to ensure sufficient supply for the body of P-i from diet. Previous experiments in humans and rodents suggest that two pathways for the absorption of P-i exist. an active transcellular P-i transport and a second paracellular pathway. Whereas the identity, role, and regulation of active P-i transport have been extensively studied, much less is known about the properties of the paracellular pathway. In Ussing chamber experiments, we characterized paracellular intestinal P-i permeabilities and fluxes. Dilution potential measurements in intestinal cell culture models demonstrated that the tight junction is permeable to P-i. with monovalent P-i having a higher permeability than divalent P-i. These findings were confirmed in rat and mouse intestinal segments by use of Ussing chambers and a combination of dilution potential measurements and fluxes of radiolabeled P-32(i). Both techniques yielded very similar results, showing that paracellular P-i fluxes were bidirectional and that P-i permeability was similar to 50% of the permeability for Na+ or Cl-. P-i fluxes were a function of the concentration gradient and P-i species (mono- vs. divalent P-i). In mice lacking the active transcellular P-i transport component sodium-dependent P-i transporter NaPi-IIb, the paracellular pathway was not upregulated. In summary. the small and large intestines have a very high paracellular P-i permeability, which may favor monovalent P-i fluxes and allow efficient uptake of P-i even in the absence of active transcellular P-i uptake. NEW & NOTEWORTHY The paracellular permeability for phosphate is high along the entire axis of the small and large intestine. There is a slight preference for monovalent phosphate. Paracellular phosphate fluxes do not increase when transcellular phosphate transport is genetically abolished. Paracellular phosphate transport may be an important target for therapies aiming to reduce intestinal phosphate absorption.